ArticleNeurobiology of disease2017
Human COMT over-expression confers a heightened susceptibility to dyskinesia in mice.
Article in Neurobiology of disease, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 22 citations in OpenAlex.
- Alx3 deficiency disrupts energy homeostasis, alters body composition, and impairs hypothalamic regulation of food intake.Cellular and molecular life sciences : CMLS · 2024Article
- Genetic meta-analysis of levodopa induced dyskinesia in Parkinson's disease.NPJ Parkinson's disease · 2023Article
- Genetic meta-analysis of levodopa induced dyskinesia in Parkinson's disease.medRxiv : the preprint server for health sciences · 2023Article
- The pathogenesis of blepharospasm.Frontiers in neurology · 2023Review
- Network Pharmacology and Metabolomics Studies on Antimigraine Mechanisms of Da Chuan Xiong Fang (DCXF).Evidence-based complementary and alternative medicine : eCAM · 2021Article
- Diabetes Causes Dysfunctional Dopamine Neurotransmission Favoring Nigrostriatal Degeneration in Mice.Movement disorders : official journal of the Movement Disorder Society · 2020Article
- Effort-related decision making in humanized COMT mice: Effects of ValPharmacology, biochemistry, and behavior · 2020Article
- RasGRP1 is a causal factor in the development of l-DOPA-induced dyskinesia in Parkinson's disease.Science advances · 2020Article
- L-DOPA in Parkinson's Disease: Looking at the "False" Neurotransmitters and Their Meaning.International journal of molecular sciences · 2019Review
- Genetic Knockdown of mGluR5 in Striatal D1R-Containing Neurons Attenuates L-DOPA-Induced Dyskinesia in Aphakia Mice.Molecular neurobiology · 2019Article
- Striatal Reinnervation Process after Acute Methamphetamine-Induced Dopaminergic Degeneration in Mice.Neurotoxicity research · 2018Article
- Dopamine receptors: homomeric and heteromeric complexes in L-DOPA-induced dyskinesia.Journal of neural transmission (Vienna, Austria : 1996) · 2018Review
- Levodopa treatment and dendritic spine pathology.Movement disorders : official journal of the Movement Disorder Society · 2018Review
- Peripheral Administration of Tetanus Toxin Hc Fragment Prevents MPPNeurotoxicity research · 2018Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Catechol-O-methyltransferase (COMT) degrades dopamine and its precursor l-DOPA and plays a critical role in regulating synaptic dopamine actions. We investigated the effects of heightened levels of COMT on dopamine-regulated motor behaviors and molecular alterations in a mouse model of dyskinesia. Transgenic mice overexpressing human COMT (TG) and their wildtype (WT) littermates received unilateral 6-OHDA lesions in the dorsal striatum and were treated chronically with l-DOPA for two weeks. l-DOPA-induced dyskinesia was exacerbated in TG mice without altering l-DOPA motor efficacy as determined by contralateral rotations or motor coordination. Inductions of FosB and phospho-acetylated histone 3 (molecular correlates of dyskinesia) were potentiated in the lesioned striatum of TG mice compared with their WT littermates. The TG mice had lower basal levels of dopamine in the striatum. In mice with lesions, l-DOPA induces a greater increase in the dopamine metabolite 3-methoxytyramine in the lesioned striatum of dyskinetic TG mice than in WT mice. The levels of serotonin and its metabolite were similar in TG and WT mice. Our results demonstrate that human COMT overexpression confers a heightened susceptibility to l-DOPA-induced dyskinesia and alters molecular and neurochemical responses in the lesioned striatum of mice.
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